Skip to main content
SpringerLink
Log in

Polymorphisms of glutathione-S-transferases M1, T1, P1 and susceptibility to colorectal cancer in a sample of the Tunisian population

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

In this study, we investigated the associations of polymorphisms in glutathione-S-transferases (GSTs) genes that are GSTM1, GSTT1, and GSTP1, with sporadic colorectal cancer (CRC). Hundred and fifty patients with CRC and 128 healthy controls were genotyped. DNA was isolated from blood samples. Polymorphisms were assessed by polymerase chain reaction–restriction fragment length polymorphism-based methods and polymerase chain reaction multiplex. Logistic regression analyses showed significant risk for CRC associated with GSTP1 homozygotes for Val-105 (OR 4.82; 95 % CI 1.97–11.80) or for individuals who possessed at least one Val-105 allele (OR 2.54; 95 % CI 1.751–3.703). There were no statistically significant differences in the frequency of GSTM1- and GSTT1-null genotypes (p > 0.05). The GSTM1-null was found in 70.47 % of all cases and 70.07 % of controls (OR 0.61; 95 % CI 0.33–1.12). The GSTT1-null genotype was found in 38.77 % of cases and 49.22 % of controls (OR 1.53; 95 % CI 0.94–2.47). No effect of any genotype for GSTM1 and GSTT1 on CRC was detected. But then an association between the polymorphism of the GSTP1 and the CRC susceptibility was detected.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, Starling N. Colorectal cancer. Lancet. 2010;375(9719):1030–47.

    Article  PubMed  Google Scholar 

  2. Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, et al. Cancer incidence in five continents. Lyon: IARC Scientific Publication; 2007. No. 160, Vol. IX, p. 107.

  3. Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol. 2005;45:51–88.

    Article  CAS  PubMed  Google Scholar 

  4. Conaway CC, Yang YM, Chung FL. Isothiocyanates as cancer chemopreventive agents: their biological activities and metabolism in rodents and humans. Curr Drug Metab. 2002;3:233–55.

    Article  CAS  PubMed  Google Scholar 

  5. Yang Y, Yan H, Li Y, Yang ST, Zhang X. Isothiocyanates from Broccolini seeds induce apoptosis in human colon cancer cells: proteomic and bioinformatic analyses. Pharmazie. 2011;66:382–90.

    CAS  PubMed  Google Scholar 

  6. Hayes JD, Strange RC. Glutathione-S-transferase polymorphisms and their biological consequences. Pharmacology. 2000;61:154–66.

    Article  CAS  PubMed  Google Scholar 

  7. Whyatt RM, Perera FP, Jedrychowski W, Santella RM, Garte S, Bell DA. Association between polycyclic aromatic hydrocarbon-DNA adduct levels in maternal and newborn white blood cells and glutathione S-transferase P1 and CYP1A1 polymorphisms. Cancer Epidemiol Biomarkers Prev. 2000;9:207–12.

    CAS  PubMed  Google Scholar 

  8. McIlwain CC, Townsend DM, Tew KD. Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene. 2006;25:1639–48.

    Article  CAS  PubMed  Google Scholar 

  9. Sachse C, Smith G, Wilkie MJ, Barrett JH, Waxman R, Sullivan F, Forman D, Bishop DT, Wolf CR. A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer. Carcinogenesis. 2002;23:1839–49.

    Article  CAS  PubMed  Google Scholar 

  10. de Jong MM, Nolte IM, te Meerman GJ, van der Graaf WTA, de Vries EGE, Sijmons RH, Hofstra RMW, Kleibeuker JH. Low-penetrance genes and their involvement in colorectal cancer susceptibility. Cancer Epidemiol Biomarkers Prev. 2002;11:1332–52.

    PubMed  Google Scholar 

  11. Houlston RS, Tomlinson IP. Polymorphisms and colorectal tumor risk. Gastroenterology. 2001;121:282–301.

    Article  CAS  PubMed  Google Scholar 

  12. Strassburg CP, Vogel A, Kneip S, Tukey RH, Manns MP. Polymorphisms of the human UDP-glucuronosyltransferase (UGT) 1A7 gene in colorectal cancer. Gut. 2002;50:851–6.

    Article  CAS  PubMed  Google Scholar 

  13. Coles BF, Chen G, Kadlubar FF, Radominska-Pandya A. Interindividual variation and organ-specific patterns of glutathione S-transferase alpha, mu, and pi expression in gastrointestinal tract mucosa of normal individuals. Arch Biochem Biophys. 2002;403:270–6.

    Article  CAS  PubMed  Google Scholar 

  14. Higgins LG, Hayes JD. Mechanisms of induction of cytosolic and microsomal glutathione transferase (GST) genes by xenobiotics and proinflammatory agents. Drug Metab Rev. 2011;43(2):92–137.

    Article  CAS  PubMed  Google Scholar 

  15. Ryberg D, Skaug V, Hewer A, Phillips DH, Harries LW, Wolf CR, Ogreid D, Ulvik A, Vu P, Haugen A. Genotypes of glutathione transferase M1 and P1 and their significance for lung DNA adduct levels and cancer risk. Carcinogenesis. 1997;18:1285–9.

    Article  CAS  PubMed  Google Scholar 

  16. Watson MA, Stewart RK, Smith GB, Massey TE, Bell DA. Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution. Carcinogenesis. 1998;19:275–80.

    Article  CAS  PubMed  Google Scholar 

  17. Brockmoller J, Kerb R, Drakoulis N, Nitz M, Roots I. Genotype and phenotype of glutathione S-transferase class mu isoenzymes mu and psi in lung cancer patients and controls. Cancer Res. 1993;53:1004–11.

    CAS  PubMed  Google Scholar 

  18. Van Der Logt EM, Bergevoet SM, Roelofs HM, Van Hooijdonk Z, Te Morsche RH, Wobbes T, De Kok JB, Nagengast FM, Peters WH. Genetic polymorphisms in UDP-glucuronosyltransferases and glutathione Stransferases and colorectal cancer risk. Carcinogenesis. 2004;25:2407–15.

    Article  PubMed  Google Scholar 

  19. Ping J, Wang H, Huang M, Liu ZS. Genetic analysis of glutathione Stransferase A1 polymorphism in the Chinese population and the influence of genotype on enzymatic properties. Toxicol Sci. 2006;89:438–43.

    Article  CAS  PubMed  Google Scholar 

  20. Chen CL, Liu Q, Relling MV. Simultaneous characterization of glutathione S-transferase M1 and T1 polymorphisms by polymerase chain reaction in American whites and blacks. Pharmacogenetics. 1997;6:187–91.

    Article  Google Scholar 

  21. Harris MJ, Coggan M, Langton L, Wilson SR, Board PG. Polymorphism of the Pi class glutathione S-transferase in normal populations and cancer patients. Pharmacogenetics. 1998;8:27–31.

    Article  CAS  PubMed  Google Scholar 

  22. Welfare M, Monesola AA, Bassendine MF, Daly AK. Polymorphisms in GSTP1, GSTM1, and GSTT1 and susceptibility to colorectal cancer. Cancer Epidemiol Biomarkers Prev. 1999;8:289–92.

    CAS  PubMed  Google Scholar 

  23. Loktionov A, Watson MA, Gunter M, Stebbings WS, Speakman CT, Bingham SA. Glutathione-S-transferase gene polymorphisms in colorectal cancer patients: interaction between GSTM1 and GSTM3 allele variants as a risk-modulating factor. Carcinogenesis. 2001;22:1053–60.

    Article  CAS  PubMed  Google Scholar 

  24. Nijhoff WA, Grubben MJA, Nagengast FM, Jansen JBMJ, Verhagen H, van Poppel G, Peters WHM. Effects of consumption of brussels sprouts on intestinal and lymphocytic glutathione and glutathione Stransferases in humans. Carcinogenesis. 1995;16:2125–8.

    Article  CAS  PubMed  Google Scholar 

  25. Economopoulos KP, Sergentanis TN. STM1, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: a comprehensive meta-analysis. Eur J Cancer. 2010;46:1617–31.

    Article  CAS  PubMed  Google Scholar 

  26. Hezova R, Bienertova-Vasku J, Sachlova M, Brezkova V, Vasku A, Svoboda M, Radová L, Kiss I, Vyzula R, Slaby O. Common polymorphisms in GSTM1, GSTT1, GSTP1, GSTA1 and susceptibility to colorectal cancer in the Central European population. Eur J Med Res. 2012;17:17.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Lampe JW, Peterson S. Brassica, biotransformation and cancer risk: genetic polymorphisms alter the preventive effects of cruciferous vegetables. J Nutr. 2002;132:2991–4.

    CAS  PubMed  Google Scholar 

  28. Butler WJ, Ryan P, Roberts-Thomson IC. Metabolic genotypes and risk for colorectal cancer. J Gastroenterol Hepatol. 2001;16:631–5.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was done in Farhat Hached Hospital, Sousse, Tunisia. It was financially supported by the hospital.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Biochemistry Laboratory, Farhat Hached University Hospital, Sousse, Tunisia

    Asma Kassab, Awatef Msolly & Abdelhédi Miled

  2. Department of Biochemistry and Molecular Biology, Pharmaceutical Faculty, Farhat Hached University Hospital, Monastir, Tunisia

    Ramzi Lakhdar

  3. Department of Medical Oncology, Farhat Hached University Hospital, Sousse, Tunisia

    Olfa Gharbi

  4. Department of Biochemistry, Dental Faculty, 5000, Monastir, Tunisia

    Awatef Msolly

Authors
  1. Asma Kassab
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Awatef Msolly
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ramzi Lakhdar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Olfa Gharbi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Abdelhédi Miled
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Awatef Msolly.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kassab, A., Msolly, A., Lakhdar, R. et al. Polymorphisms of glutathione-S-transferases M1, T1, P1 and susceptibility to colorectal cancer in a sample of the Tunisian population. Med Oncol 31, 760 (2014). https://doi.org/10.1007/s12032-013-0760-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-013-0760-z

Keywords

Search

Navigation